Object
Title: Platelet studies using aptamers and the flow quartz crystal microbalance with dissipation monitoring system
Abstract:
Platelet-related pathologies play a vital role in the development of cardiovascular diseases. Thus, there is a need for a deeper understanding of platelet-dependent pathophysiological mechanisms. It was assumed that some unique aspects of platelet activity could be uncovered by applying novel methodologies and experimental tools. In the first part of this dissertation, the pharmacological studies of platelets were described using the selective anti-thrombin HD1 and HD22 aptamers interacting with distinct ligand-binding exosite I and exosite II of the thrombin molecule. In the second part of this work, the effect of endothelial mediators on platelet mechanoadhesion to fibrinogen under flow conditions was described using a gravimetric-acoustic flow Quartz Crystal Microbalance with Dissipation monitoring system (QCM-D). Modulation of thrombin activity, the most potent platelet agonist, by HD1 and HD22 aptamers was examined directly with the platelet aggregation assay, platelet-poor plasma, and the whole human blood-based assays. It was shown that aptamer HD1 had a broad antithrombin profile in contrast to aptamer HD22. By comparing the effects of HD1 and HD22 aptamers, the functional differences in the regulation of thrombin activity dependent on their binding site in the thrombin molecule were identified. Using a broad methodological approach, includin ; g the analysis of platelet aggregation, as well as the studies of thrombinogenesis, fibrinogenesis, and thrombus formation in whole blood under flow conditions, the effectiveness and difference in activity profiles of the HD1 and HD22 anti-thrombin aptamers were evaluated, and the substantial cognitive and application potential of aptapharmacology was identified. The research reported within the second part of this dissertation concentrated on the study of platelet-involving primary hemostasis, which requires the application of several highly sensitive methods. In particular, the mechanisms of mechanoadhesion, a biomechanical phenomenon whose nature cannot be fully explained using only classical experimental methods of platelet testing, were studied. The research conducted using the QCM-D system has shown that the effects of selected endothelial mediators, i.e., prostacyclin (PGI2), nitric oxide (NO), and carbon monoxide (CO), resulted in different biomechanical platelet responses during their adhesion to fibrinogen. The dependence of platelet viscoelastic properties on the endothelial mediator applied was reflected in a different platelet morphology imaged by SEM microscopy.
Place of publishing:
Level of degree:
Degree grantor:
Rada Dyscypliny Nauki medyczne
Promoter:
Chłopicki, Stefan ; Nowakowska, Maria
Date issued:
Identifier:
Language:
Access rights:
Object collections:
Last modified:
Apr 15, 2024
In our library since:
Apr 15, 2024
Number of object content hits:
0
Number of object content views in PDF format
0
All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/5080
Show description in RDF format:
Show description in OAI-PMH format:
| Edition name | Date |
|---|---|
| UJCMf5dc15a8f20346db92ca778fd18c2ae7 | Apr 15, 2024 |
Objects
Similar
Derszniak, Katarzyna
Dyszkiewicz-Korpanty, Anna
Gwóźdź, Paweł
Węgrzyn, Wojciech
Przyborowski, Kamil
Baj-Krzyworzeka, Monika
Grzybczak, Rafał
Kostka,Barbara Lipiński,Zbigniew
